3026 lines
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Entry
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- *615944 - C2 CALCIUM-DEPENDENT DOMAIN-CONTAINING PROTEIN 3; C2CD3
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- OMIM
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<p>
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<span class="h4">*615944</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/615944">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000168014;t=ENST00000334126" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=26005" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=615944" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000168014;t=ENST00000334126" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001286577,NM_015531" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001286577" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=615944" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.proteinatlas.org/search/C2CD3" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/5262712,21739433,21749758,21750598,23272593,34532160,72069061,77999864,84570013,148596944,313104297,557440801" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q4AC94" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=26005" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000168014;t=ENST00000334126" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=C2CD3" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=C2CD3" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+26005" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/C2CD3" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:26005" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/26005" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr11&hgg_gene=ENST00000334126.12&hgg_start=74012718&hgg_end=74171002&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:24564" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=615944[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=615944[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/C2CD3/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000168014" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=C2CD3" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=C2CD3" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=C2CD3" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=C2CD3&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA162379082" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:24564" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0052425.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2142166" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/C2CD3#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:2142166" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/26005/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=26005" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060503-104" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=C2CD3&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 763837007<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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615944
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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C2 CALCIUM-DEPENDENT DOMAIN-CONTAINING PROTEIN 3; C2CD3
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=C2CD3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">C2CD3</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/11/742?start=-3&limit=10&highlight=742">11q13.4</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:74012718-74171002&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">11:74,012,718-74,171,002</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/11/742?start=-3&limit=10&highlight=742">
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11q13.4
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Orofaciodigital syndrome XIV
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615948"> 615948 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/615944" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/615944" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Based on experiments in mice, C2CD3 is predicted to be an essential regulator of cilia formation, hedgehog signaling (see SHH, <a href="/entry/600725">600725</a>), and embryonic patterning (<a href="#3" class="mim-tip-reference" title="Hoover, A. N., Wynkoop, A., Zeng, H., Jia, J., Niswander, L. A., Liu, A. <strong>C2cd3 is required for cilia formation and Hedgehog signaling in mouse.</strong> Development 135: 4049-4058, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19004860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19004860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19004860[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1242/dev.029835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19004860">Hoover et al., 2008</a>). C2CD3 is also a positive regulator of centriole length (<a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24997988+19004860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Hoover, A. N., Wynkoop, A., Zeng, H., Jia, J., Niswander, L. A., Liu, A. <strong>C2cd3 is required for cilia formation and Hedgehog signaling in mouse.</strong> Development 135: 4049-4058, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19004860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19004860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19004860[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1242/dev.029835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19004860">Hoover et al. (2008)</a> cloned mouse C2cd3. The deduced 2,322-amino acid protein has a calculated molecular mass of approximately 250 kD. It has 5 C2 domains predicted to mediate interactions with proteins and membrane lipids. C2cd3 was expressed ubiquitously in mouse embryos between embryonic day 8.5 (E8.5) and E10.5. Fluorescence-tagged C2cd3 localized to the ciliary basal body in transfected mouse embryonic fibroblasts (MEFs). Orthologs of C2cd3 were detected in vertebrates, including human, but not in invertebrates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19004860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al. (2014)</a> reported that C2CD3 contains a C2-like N-terminal domain, followed by 6 canonical C2 domains predicted to bind calcium and phospholipid headgroups. Fluorescence-tagged mouse C2cd3 localized to centriolar satellites and to the distal lumen of mature centrioles and procentrioles, near the distal tip. Database analysis revealed orthologs of C2CD3 in organisms that assemble centrioles or cilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#3" class="mim-tip-reference" title="Hoover, A. N., Wynkoop, A., Zeng, H., Jia, J., Niswander, L. A., Liu, A. <strong>C2cd3 is required for cilia formation and Hedgehog signaling in mouse.</strong> Development 135: 4049-4058, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19004860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19004860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19004860[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1242/dev.029835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19004860">Hoover et al. (2008)</a> mapped the C2CD3 gene to human chromosome 11q13.4 and mouse chromosome 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19004860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using coimmunoprecipitation analysis, <a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al. (2014)</a> found that endogenous C2CD3 interacted with OFD1 (<a href="/entry/300170">300170</a>) in human RPE cells. Epitope-tagged human OFD1 also interacted with fluorescence-tagged mouse C2cd3 in vitro. RPE cells overexpressing fluorescence-tagged mouse C2cd3 developed hyperelongated centrioles and centriole-like microtubular rods in various regions of the cytoplasm. Coexpression of mouse Ofd1 with C2cd3 reduced the frequency of hyperelongated centrioles in transfected U2OS cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using wildtype and C2cd3-null MEFs, <a href="#6" class="mim-tip-reference" title="Ye, X., Zeng, H., Ning, G., Reiter, J. F., Liu, A. <strong>C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals.</strong> Proc. Nat. Acad. Sci. 111: 2164-2169, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24469809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24469809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24469809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1318737111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24469809">Ye et al. (2014)</a> determined that localization of C2cd3 to centriolar satellites depended on Pcm1 (<a href="/entry/600299">600299</a>) and dynein (see <a href="/entry/600112">600112</a>)-mediated retrograde transport. Localization of C2cd3 to distal ends of the mother and daughter centrioles was required for recruitment of the distal appendage proteins Ccdc41 (CEP83; <a href="/entry/615847">615847</a>), Sclt1 (<a href="/entry/611399">611399</a>), Cep89 (<a href="/entry/615470">615470</a>), Fbf1 (<a href="/entry/616807">616807</a>), and Cep164 (<a href="/entry/614848">614848</a>) and for the intraflagellar transport B proteins Ift88 (<a href="/entry/600595">600595</a>) and Ift52 (<a href="/entry/617094">617094</a>). In the absence of C2cd3, Ttbk2 (<a href="/entry/611695">611695</a>) was not recruited to the distal end of the mother centriole, and Cp110 (<a href="/entry/609544">609544</a>) was not removed. C2cd3 was also required for docking of ciliary vesicles to the mother centriole. <a href="#6" class="mim-tip-reference" title="Ye, X., Zeng, H., Ning, G., Reiter, J. F., Liu, A. <strong>C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals.</strong> Proc. Nat. Acad. Sci. 111: 2164-2169, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24469809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24469809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24469809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1318737111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24469809">Ye et al. (2014)</a> concluded that C2CD3 regulates initiation of ciliogenesis through centriolar maturation, ciliogenic protein recruitment, and ciliary vesicle docking. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24469809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 4-year-old boy with orofaciodigital syndrome (OFD14; <a href="/entry/615948">615948</a>), <a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al. (2014)</a> identified a homozygous truncating mutation in the C2CD3 gene (R62X; <a href="#0001">615944.0001</a>). The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Sequencing of the coding exons of C2CD3 in 34 patients with OFD identified 1 fetus who was compound heterozygous for 2 mutations in the C2CD3 gene (<a href="#0002">615944.0002</a> and <a href="#0003">615944.0003</a>). Functional studies of the 3 variants were not performed, but <a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al. (2014)</a> demonstrated that C2CD3 is required for cilium assembly and function, consistent with OFD being a ciliopathy. Moreover, hypomorphic or null mutations in this gene in mice cause a phenotype consistent with a ciliopathy (see ANIMAL MODEL). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>From a cohort of 43 French Canadian patients from 35 families diagnosed with Joubert syndrome (see <a href="/entry/213300">213300</a>), <a href="#4" class="mim-tip-reference" title="Srour, M., Hamdan, F. F., McKnight, D., Davis, E., Mandel, H., Schwartzentruber, J., Martin, B., Patry, L., Nassif, C., Dionne-Laporte, A., Ospina, L. H., Lemyre, E., and 22 others. <strong>Joubert syndrome in French Canadians and identification of mutations in CEP104.</strong> Am. J. Hum. Genet. 97: 744-753, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26477546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26477546</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.09.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26477546">Srour et al. (2015)</a> identified 2 sibs (family 472) who were compound heterozygous for a missense (G1743C) and a nonsense (R1977X) mutation in the C2CD3 gene. The patients exhibited MTS and severe global developmental delay with hypotonia and ataxia, but information regarding oral, facial, and digital features was not reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26477546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 fetuses with a 'skeletal ciliopathy' from a Lebanese-Palestinian family, <a href="#2" class="mim-tip-reference" title="Cortes, C. R., McInerney-Leo, A. M., Vogel, I., Rondon Galeano, M. C., Leo, P. J., Harris, J. E., Anderson, L. K., Keith, P. A., Brown, M. A., Ramsing, M., Duncan, E. L., Zankl, A., Wicking, C. <strong>Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function.</strong> Sci. Rep. 6: 24083, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27094867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27094867</a>] [<a href="https://doi.org/10.1038/srep24083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27094867">Cortes et al. (2016)</a> identified compound heterozygous mutations in C2CD3, W65C a I477X. Analysis of patient fibroblasts under ciliogenic conditions showed a reduction in the percentage of cells with a cilium compared to controls. In addition, there was a defect in localization of IFT88 (<a href="/entry/600595">600595</a>) at the centrioles in the nonciliated cells, and CP110 (CCP110; <a href="/entry/609544">609544</a>) was not efficiently removed from the mother centriole in patient cells. The authors noted that the defect in uncapping the mother centriole involves one of the earliest steps in ciliogenesis which, together with the inability to correctly localize IFT88, represents a block to the subsequent steps in ciliogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27094867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 children from 3 unrelated 'ciliopathy pedigrees,' <a href="#1" class="mim-tip-reference" title="Boczek, N. J., Hopp, K., Benoit, L., Kraft, D., Cousin, M. A., Blackburn, P. R., Madsen, C. D., Oliver, G. R., Nair, A. A., Na, J., Bianchi, D. W., Beek, G., Harris, P. C., Pichurin, P., Klee, E. W. <strong>Characterization of three ciliopathy pedigrees expands the phenotype associated with biallelic C2CD3 variants.</strong> Europ. J. Hum. Genet. 26: 1797-1809, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30097616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30097616</a>] [<a href="https://doi.org/10.1038/s41431-018-0222-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30097616">Boczek et al. (2018)</a> performed whole-exome sequencing and identified compound heterozygous mutations in the C2CD3 gene in all (see, e.g., <a href="#0004">615944.0004</a> and <a href="#0005">615944.0005</a>). The unaffected parents were each heterozygous for 1 of the mutations, which were either not present or present at extremely low frequency (less than 0.001%) in the gnomAD database. Noting the phenotypic diversity exhibited by their patients, the authors concluded that biallelic variants in C2CD3 can cause a spectrum of ciliopathy disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30097616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a genetic screen in mice, <a href="#3" class="mim-tip-reference" title="Hoover, A. N., Wynkoop, A., Zeng, H., Jia, J., Niswander, L. A., Liu, A. <strong>C2cd3 is required for cilia formation and Hedgehog signaling in mouse.</strong> Development 135: 4049-4058, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19004860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19004860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19004860[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1242/dev.029835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19004860">Hoover et al. (2008)</a> identified 'hearty' (hty), a recessive mutation that disrupted embryonic development and caused lethality between E11 and E13. Some hty/hty mutants exhibited exencephaly in the midbrain and posterior forebrain, a twisted body axis, right heart looping, and pericardial edema. Hty/hty mutants that underwent neural tube closure presented with a tight mesencephalic flexure. At E12.5, all hty/hty mutants exhibited severe polydactyly in all 4 limbs. Nodal (<a href="/entry/601265">601265</a>) and Lefty2 (<a href="/entry/601877">601877</a>) were expressed in both left and right lateral plate mesoderm, suggesting loss of left-right asymmetry. <a href="#3" class="mim-tip-reference" title="Hoover, A. N., Wynkoop, A., Zeng, H., Jia, J., Niswander, L. A., Liu, A. <strong>C2cd3 is required for cilia formation and Hedgehog signaling in mouse.</strong> Development 135: 4049-4058, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19004860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19004860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19004860[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1242/dev.029835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19004860">Hoover et al. (2008)</a> identified the hty mutation as a C-to-A transversion at the first nucleotide of intron 4 of the C2cd3 gene, resulting in disrupted splicing and truncation of the C2cd3 protein. Homozygous disruption of C2cd3 via gene trap (gt) insertion resulted in a similar phenotype, as did hty/gt transheterozygosity. Ventral node cells of hty/hty and gt/gt embryos and hty/hty MEFs showed disrupted cilia formation. Immunofluorescence analysis, Western blot analysis, and gene expression profiling revealed disrupted patterning, processing, and expression of proteins involved in hedgehog signaling in C2cd3 mutant embryos. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19004860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunofluorescence analysis and electron microscopy, <a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al. (2014)</a> showed that centriolar distal appendages and subdistal appendages were absent from hty/hty and C2cd3-null mouse embryonic fibroblasts. C2cd3 mutant centrioles, which were shorter than wildtype, also showed reduced Ofd1 content. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=615944[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<p>In a boy, born of consanguineous parents, with orofaciodigital syndrome XIV (OFD14; <a href="/entry/615948">615948</a>), <a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al. (2014)</a> identified a homozygous c.184C-T transition in exon 2 of the C2CD3 gene, resulting in an arg62-to-ter (R62X) substitution. The mutation was found by a combination of homozygosity mapping and exome sequencing and was confirmed by Sanger sequencing. The mutation segregated with the disorder in the family was not present in the Exome Variant Server database. Functional studies of this variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs587777654 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777654;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs587777654?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs587777654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs587777654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a male fetus with orofaciodigital syndrome XIV (OFD14; <a href="/entry/615948">615948</a>), <a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al. (2014)</a> identified 2 compound heterozygous mutations in the C2CD3 gene: a c.3085T-G transversion in exon 17, resulting in a cys1029-to-gly (C1029G) substitution, and an A-to-T transversion in the splice acceptor site of intron 21 (c.3911-2A-T; <a href="#0003">615944.0003</a>), resulting in a splice site mutation, a 4-bp frameshift deletion (c.3911_3914delCAAG), and premature termination (Ala1304ValfsTer3). Each unaffected parent was heterozygous for 1 of the mutations. This patient was ascertained from a cohort of 34 individuals with OFD who were screened for mutations in the coding exons of C2CD3. Neither mutation was found in the Exome Variant Server database. Functional studies were not performed on these variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs149366137 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs149366137;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs149366137?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs149366137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs149366137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000133547 OR RCV001849965" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000133547, RCV001849965" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000133547...</a>
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<p>For discussion of the splice site mutation in the C2CD3 gene (c.3911-2A-T) that was found in compound heterozygous state in a fetus with orofaciodigital syndrome XIV (OFD14; <a href="/entry/615948">615948</a>) by <a href="#5" class="mim-tip-reference" title="Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others. <strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong> Nature Genet. 46: 905-911, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24997988">Thauvin-Robinet et al. (2014)</a>, see <a href="#0002">615944.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 OROFACIODIGITAL SYNDROME XIV</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1174615027 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1174615027;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1174615027?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1174615027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1174615027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000766221 OR RCV002533921" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000766221, RCV002533921" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000766221...</a>
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<p>In 2 sibs (family 1) with orofaciodigital syndrome XIV (OFD14; <a href="/entry/615948">615948</a>), <a href="#1" class="mim-tip-reference" title="Boczek, N. J., Hopp, K., Benoit, L., Kraft, D., Cousin, M. A., Blackburn, P. R., Madsen, C. D., Oliver, G. R., Nair, A. A., Na, J., Bianchi, D. W., Beek, G., Harris, P. C., Pichurin, P., Klee, E. W. <strong>Characterization of three ciliopathy pedigrees expands the phenotype associated with biallelic C2CD3 variants.</strong> Europ. J. Hum. Genet. 26: 1797-1809, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30097616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30097616</a>] [<a href="https://doi.org/10.1038/s41431-018-0222-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30097616">Boczek et al. (2018)</a> identified compound heterozygosity for splicing mutations in the C2CD3 gene: a c.1365+1G-A transition (c.1365+1G-A, NM_001286577.1) in intron 8, and a c.5090+5G-C transversion in intron 25, both predicted to result in premature termination codons (Ser406ArgfsTer23 and Ser1652TyrfsTer26, respectively). The unaffected parents were each heterozygous for 1 of the mutations; the first variant was present in the gnomAD database at a minor allele frequency of 0.000004, whereas the second was not found in the gnomAD database. Sashimi plot analysis of RNA sequencing data showed that the c.1365+1G-A variant caused skipping of exon 8 in 28% of reads, resulting in the truncated Ser406ArgfsTer23 protein, and the c.5090+5G-C variant caused skipping of exon 25 in 35% of reads, resulting in the truncated Ser1652TyrfsTer26 protein. Experiments with puromycin provided evidence that the out-of-frame transcripts undergo nonsense-mediated decay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30097616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1565237232 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1565237232;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1565237232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1565237232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000766222" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000766222" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000766222</a>
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<p>For discussion of the c.5090+5G-C transversion (c.5090+5G-C, NM_001286577.1) in intron 25 of the C2CD3 gene, predicted to result in a premature termination codon (Ser1652TyrfsTer26), that was found in compound heterozygous state in a patient with orofaciodigital syndrome XIV (OFD14; <a href="/entry/615948">615948</a>) by <a href="#1" class="mim-tip-reference" title="Boczek, N. J., Hopp, K., Benoit, L., Kraft, D., Cousin, M. A., Blackburn, P. R., Madsen, C. D., Oliver, G. R., Nair, A. A., Na, J., Bianchi, D. W., Beek, G., Harris, P. C., Pichurin, P., Klee, E. W. <strong>Characterization of three ciliopathy pedigrees expands the phenotype associated with biallelic C2CD3 variants.</strong> Europ. J. Hum. Genet. 26: 1797-1809, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30097616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30097616</a>] [<a href="https://doi.org/10.1038/s41431-018-0222-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30097616">Boczek et al. (2018)</a>, see <a href="#0004">615944.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30097616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Boczek, N. J., Hopp, K., Benoit, L., Kraft, D., Cousin, M. A., Blackburn, P. R., Madsen, C. D., Oliver, G. R., Nair, A. A., Na, J., Bianchi, D. W., Beek, G., Harris, P. C., Pichurin, P., Klee, E. W.
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<strong>Characterization of three ciliopathy pedigrees expands the phenotype associated with biallelic C2CD3 variants.</strong>
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Europ. J. Hum. Genet. 26: 1797-1809, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30097616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30097616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30097616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41431-018-0222-3" target="_blank">Full Text</a>]
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Cortes, C. R., McInerney-Leo, A. M., Vogel, I., Rondon Galeano, M. C., Leo, P. J., Harris, J. E., Anderson, L. K., Keith, P. A., Brown, M. A., Ramsing, M., Duncan, E. L., Zankl, A., Wicking, C.
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<strong>Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function.</strong>
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Sci. Rep. 6: 24083, 2016. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27094867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27094867</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27094867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/srep24083" target="_blank">Full Text</a>]
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Hoover, A. N., Wynkoop, A., Zeng, H., Jia, J., Niswander, L. A., Liu, A.
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<strong>C2cd3 is required for cilia formation and Hedgehog signaling in mouse.</strong>
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Development 135: 4049-4058, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19004860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19004860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19004860[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19004860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1242/dev.029835" target="_blank">Full Text</a>]
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Srour, M., Hamdan, F. F., McKnight, D., Davis, E., Mandel, H., Schwartzentruber, J., Martin, B., Patry, L., Nassif, C., Dionne-Laporte, A., Ospina, L. H., Lemyre, E., and 22 others.
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<strong>Joubert syndrome in French Canadians and identification of mutations in CEP104.</strong>
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Am. J. Hum. Genet. 97: 744-753, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26477546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26477546</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26477546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2015.09.009" target="_blank">Full Text</a>]
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Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others.
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<strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong>
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Nature Genet. 46: 905-911, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24997988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.3031" target="_blank">Full Text</a>]
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Ye, X., Zeng, H., Ning, G., Reiter, J. F., Liu, A.
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<strong>C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals.</strong>
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Proc. Nat. Acad. Sci. 111: 2164-2169, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24469809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24469809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24469809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24469809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.1318737111" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 04/05/2019
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Patricia A. Hartz - updated : 8/21/2014<br>Cassandra L. Kniffin - updated : 8/20/2014
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 8/18/2014
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</span>
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</div>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 04/05/2019
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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mgross : 08/25/2016<br>mgross : 02/10/2016<br>mcolton : 5/8/2015<br>mgross : 8/21/2014<br>carol : 8/21/2014<br>mcolton : 8/21/2014<br>mcolton : 8/21/2014<br>ckniffin : 8/20/2014<br>mgross : 8/19/2014<br>mcolton : 8/18/2014
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<h3>
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<span class="mim-font">
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<strong>*</strong> 615944
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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C2 CALCIUM-DEPENDENT DOMAIN-CONTAINING PROTEIN 3; C2CD3
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</h3>
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</div>
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<div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: C2CD3</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 763837007;
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</span>
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</p>
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<br />
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 11q13.4
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Genomic coordinates <span class="small">(GRCh38)</span> : 11:74,012,718-74,171,002 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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11q13.4
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</span>
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</td>
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<td>
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<span class="mim-font">
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Orofaciodigital syndrome XIV
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</span>
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</td>
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<td>
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<span class="mim-font">
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615948
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Based on experiments in mice, C2CD3 is predicted to be an essential regulator of cilia formation, hedgehog signaling (see SHH, 600725), and embryonic patterning (Hoover et al., 2008). C2CD3 is also a positive regulator of centriole length (Thauvin-Robinet et al., 2014). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hoover et al. (2008) cloned mouse C2cd3. The deduced 2,322-amino acid protein has a calculated molecular mass of approximately 250 kD. It has 5 C2 domains predicted to mediate interactions with proteins and membrane lipids. C2cd3 was expressed ubiquitously in mouse embryos between embryonic day 8.5 (E8.5) and E10.5. Fluorescence-tagged C2cd3 localized to the ciliary basal body in transfected mouse embryonic fibroblasts (MEFs). Orthologs of C2cd3 were detected in vertebrates, including human, but not in invertebrates. </p><p>Thauvin-Robinet et al. (2014) reported that C2CD3 contains a C2-like N-terminal domain, followed by 6 canonical C2 domains predicted to bind calcium and phospholipid headgroups. Fluorescence-tagged mouse C2cd3 localized to centriolar satellites and to the distal lumen of mature centrioles and procentrioles, near the distal tip. Database analysis revealed orthologs of C2CD3 in organisms that assemble centrioles or cilia. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Hoover et al. (2008) mapped the C2CD3 gene to human chromosome 11q13.4 and mouse chromosome 7. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using coimmunoprecipitation analysis, Thauvin-Robinet et al. (2014) found that endogenous C2CD3 interacted with OFD1 (300170) in human RPE cells. Epitope-tagged human OFD1 also interacted with fluorescence-tagged mouse C2cd3 in vitro. RPE cells overexpressing fluorescence-tagged mouse C2cd3 developed hyperelongated centrioles and centriole-like microtubular rods in various regions of the cytoplasm. Coexpression of mouse Ofd1 with C2cd3 reduced the frequency of hyperelongated centrioles in transfected U2OS cells. </p><p>Using wildtype and C2cd3-null MEFs, Ye et al. (2014) determined that localization of C2cd3 to centriolar satellites depended on Pcm1 (600299) and dynein (see 600112)-mediated retrograde transport. Localization of C2cd3 to distal ends of the mother and daughter centrioles was required for recruitment of the distal appendage proteins Ccdc41 (CEP83; 615847), Sclt1 (611399), Cep89 (615470), Fbf1 (616807), and Cep164 (614848) and for the intraflagellar transport B proteins Ift88 (600595) and Ift52 (617094). In the absence of C2cd3, Ttbk2 (611695) was not recruited to the distal end of the mother centriole, and Cp110 (609544) was not removed. C2cd3 was also required for docking of ciliary vesicles to the mother centriole. Ye et al. (2014) concluded that C2CD3 regulates initiation of ciliogenesis through centriolar maturation, ciliogenic protein recruitment, and ciliary vesicle docking. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a 4-year-old boy with orofaciodigital syndrome (OFD14; 615948), Thauvin-Robinet et al. (2014) identified a homozygous truncating mutation in the C2CD3 gene (R62X; 615944.0001). The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Sequencing of the coding exons of C2CD3 in 34 patients with OFD identified 1 fetus who was compound heterozygous for 2 mutations in the C2CD3 gene (615944.0002 and 615944.0003). Functional studies of the 3 variants were not performed, but Thauvin-Robinet et al. (2014) demonstrated that C2CD3 is required for cilium assembly and function, consistent with OFD being a ciliopathy. Moreover, hypomorphic or null mutations in this gene in mice cause a phenotype consistent with a ciliopathy (see ANIMAL MODEL). </p><p>From a cohort of 43 French Canadian patients from 35 families diagnosed with Joubert syndrome (see 213300), Srour et al. (2015) identified 2 sibs (family 472) who were compound heterozygous for a missense (G1743C) and a nonsense (R1977X) mutation in the C2CD3 gene. The patients exhibited MTS and severe global developmental delay with hypotonia and ataxia, but information regarding oral, facial, and digital features was not reported. </p><p>In 2 fetuses with a 'skeletal ciliopathy' from a Lebanese-Palestinian family, Cortes et al. (2016) identified compound heterozygous mutations in C2CD3, W65C a I477X. Analysis of patient fibroblasts under ciliogenic conditions showed a reduction in the percentage of cells with a cilium compared to controls. In addition, there was a defect in localization of IFT88 (600595) at the centrioles in the nonciliated cells, and CP110 (CCP110; 609544) was not efficiently removed from the mother centriole in patient cells. The authors noted that the defect in uncapping the mother centriole involves one of the earliest steps in ciliogenesis which, together with the inability to correctly localize IFT88, represents a block to the subsequent steps in ciliogenesis. </p><p>In 5 children from 3 unrelated 'ciliopathy pedigrees,' Boczek et al. (2018) performed whole-exome sequencing and identified compound heterozygous mutations in the C2CD3 gene in all (see, e.g., 615944.0004 and 615944.0005). The unaffected parents were each heterozygous for 1 of the mutations, which were either not present or present at extremely low frequency (less than 0.001%) in the gnomAD database. Noting the phenotypic diversity exhibited by their patients, the authors concluded that biallelic variants in C2CD3 can cause a spectrum of ciliopathy disorders. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a genetic screen in mice, Hoover et al. (2008) identified 'hearty' (hty), a recessive mutation that disrupted embryonic development and caused lethality between E11 and E13. Some hty/hty mutants exhibited exencephaly in the midbrain and posterior forebrain, a twisted body axis, right heart looping, and pericardial edema. Hty/hty mutants that underwent neural tube closure presented with a tight mesencephalic flexure. At E12.5, all hty/hty mutants exhibited severe polydactyly in all 4 limbs. Nodal (601265) and Lefty2 (601877) were expressed in both left and right lateral plate mesoderm, suggesting loss of left-right asymmetry. Hoover et al. (2008) identified the hty mutation as a C-to-A transversion at the first nucleotide of intron 4 of the C2cd3 gene, resulting in disrupted splicing and truncation of the C2cd3 protein. Homozygous disruption of C2cd3 via gene trap (gt) insertion resulted in a similar phenotype, as did hty/gt transheterozygosity. Ventral node cells of hty/hty and gt/gt embryos and hty/hty MEFs showed disrupted cilia formation. Immunofluorescence analysis, Western blot analysis, and gene expression profiling revealed disrupted patterning, processing, and expression of proteins involved in hedgehog signaling in C2cd3 mutant embryos. </p><p>Using immunofluorescence analysis and electron microscopy, Thauvin-Robinet et al. (2014) showed that centriolar distal appendages and subdistal appendages were absent from hty/hty and C2cd3-null mouse embryonic fibroblasts. C2cd3 mutant centrioles, which were shorter than wildtype, also showed reduced Ofd1 content. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>5 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 OROFACIODIGITAL SYNDROME XIV</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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C2CD3, ARG62TER
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<br />
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SNP: rs587777653,
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gnomAD: rs587777653,
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ClinVar: RCV000133545, RCV000201616
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a boy, born of consanguineous parents, with orofaciodigital syndrome XIV (OFD14; 615948), Thauvin-Robinet et al. (2014) identified a homozygous c.184C-T transition in exon 2 of the C2CD3 gene, resulting in an arg62-to-ter (R62X) substitution. The mutation was found by a combination of homozygosity mapping and exome sequencing and was confirmed by Sanger sequencing. The mutation segregated with the disorder in the family was not present in the Exome Variant Server database. Functional studies of this variant were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 OROFACIODIGITAL SYNDROME XIV</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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C2CD3, CYS1029GLY
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<br />
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SNP: rs587777654,
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gnomAD: rs587777654,
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ClinVar: RCV000133546
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a male fetus with orofaciodigital syndrome XIV (OFD14; 615948), Thauvin-Robinet et al. (2014) identified 2 compound heterozygous mutations in the C2CD3 gene: a c.3085T-G transversion in exon 17, resulting in a cys1029-to-gly (C1029G) substitution, and an A-to-T transversion in the splice acceptor site of intron 21 (c.3911-2A-T; 615944.0003), resulting in a splice site mutation, a 4-bp frameshift deletion (c.3911_3914delCAAG), and premature termination (Ala1304ValfsTer3). Each unaffected parent was heterozygous for 1 of the mutations. This patient was ascertained from a cohort of 34 individuals with OFD who were screened for mutations in the coding exons of C2CD3. Neither mutation was found in the Exome Variant Server database. Functional studies were not performed on these variants. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 OROFACIODIGITAL SYNDROME XIV</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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C2CD3, IVS21AS, A-T, -2
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<br />
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SNP: rs149366137,
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gnomAD: rs149366137,
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ClinVar: RCV000133547, RCV001849965
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the splice site mutation in the C2CD3 gene (c.3911-2A-T) that was found in compound heterozygous state in a fetus with orofaciodigital syndrome XIV (OFD14; 615948) by Thauvin-Robinet et al. (2014), see 615944.0002. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 OROFACIODIGITAL SYNDROME XIV</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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C2CD3, IVS8, G-A, +1
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<br />
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SNP: rs1174615027,
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gnomAD: rs1174615027,
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ClinVar: RCV000766221, RCV002533921
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</span>
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</div>
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<span class="mim-text-font">
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<p>In 2 sibs (family 1) with orofaciodigital syndrome XIV (OFD14; 615948), Boczek et al. (2018) identified compound heterozygosity for splicing mutations in the C2CD3 gene: a c.1365+1G-A transition (c.1365+1G-A, NM_001286577.1) in intron 8, and a c.5090+5G-C transversion in intron 25, both predicted to result in premature termination codons (Ser406ArgfsTer23 and Ser1652TyrfsTer26, respectively). The unaffected parents were each heterozygous for 1 of the mutations; the first variant was present in the gnomAD database at a minor allele frequency of 0.000004, whereas the second was not found in the gnomAD database. Sashimi plot analysis of RNA sequencing data showed that the c.1365+1G-A variant caused skipping of exon 8 in 28% of reads, resulting in the truncated Ser406ArgfsTer23 protein, and the c.5090+5G-C variant caused skipping of exon 25 in 35% of reads, resulting in the truncated Ser1652TyrfsTer26 protein. Experiments with puromycin provided evidence that the out-of-frame transcripts undergo nonsense-mediated decay. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 OROFACIODIGITAL SYNDROME XIV</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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C2CD3, IVS25, G-C, +5
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<br />
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SNP: rs1565237232,
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ClinVar: RCV000766222
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.5090+5G-C transversion (c.5090+5G-C, NM_001286577.1) in intron 25 of the C2CD3 gene, predicted to result in a premature termination codon (Ser1652TyrfsTer26), that was found in compound heterozygous state in a patient with orofaciodigital syndrome XIV (OFD14; 615948) by Boczek et al. (2018), see 615944.0004. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Boczek, N. J., Hopp, K., Benoit, L., Kraft, D., Cousin, M. A., Blackburn, P. R., Madsen, C. D., Oliver, G. R., Nair, A. A., Na, J., Bianchi, D. W., Beek, G., Harris, P. C., Pichurin, P., Klee, E. W.
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<strong>Characterization of three ciliopathy pedigrees expands the phenotype associated with biallelic C2CD3 variants.</strong>
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Europ. J. Hum. Genet. 26: 1797-1809, 2018.
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[PubMed: 30097616]
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[Full Text: https://doi.org/10.1038/s41431-018-0222-3]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Cortes, C. R., McInerney-Leo, A. M., Vogel, I., Rondon Galeano, M. C., Leo, P. J., Harris, J. E., Anderson, L. K., Keith, P. A., Brown, M. A., Ramsing, M., Duncan, E. L., Zankl, A., Wicking, C.
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<strong>Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function.</strong>
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Sci. Rep. 6: 24083, 2016. Note: Electronic Article.
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[PubMed: 27094867]
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[Full Text: https://doi.org/10.1038/srep24083]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hoover, A. N., Wynkoop, A., Zeng, H., Jia, J., Niswander, L. A., Liu, A.
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<strong>C2cd3 is required for cilia formation and Hedgehog signaling in mouse.</strong>
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Development 135: 4049-4058, 2008.
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[PubMed: 19004860]
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[Full Text: https://doi.org/10.1242/dev.029835]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Srour, M., Hamdan, F. F., McKnight, D., Davis, E., Mandel, H., Schwartzentruber, J., Martin, B., Patry, L., Nassif, C., Dionne-Laporte, A., Ospina, L. H., Lemyre, E., and 22 others.
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<strong>Joubert syndrome in French Canadians and identification of mutations in CEP104.</strong>
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Am. J. Hum. Genet. 97: 744-753, 2015.
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[PubMed: 26477546]
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[Full Text: https://doi.org/10.1016/j.ajhg.2015.09.009]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Thauvin-Robinet, C., Lee, J. S., Lopez, E., Herranz-Perez, V., Shida, T., Franco, B., Jego, L., Ye, F., Pasquier, L., Loget, P., Gigot, N., Aral, B., and 17 others.
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<strong>The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.</strong>
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Nature Genet. 46: 905-911, 2014.
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[PubMed: 24997988]
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[Full Text: https://doi.org/10.1038/ng.3031]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ye, X., Zeng, H., Ning, G., Reiter, J. F., Liu, A.
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<strong>C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals.</strong>
|
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Proc. Nat. Acad. Sci. 111: 2164-2169, 2014.
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[PubMed: 24469809]
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[Full Text: https://doi.org/10.1073/pnas.1318737111]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 04/05/2019<br>Patricia A. Hartz - updated : 8/21/2014<br>Cassandra L. Kniffin - updated : 8/20/2014
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</span>
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<span class="mim-text-font">
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Patricia A. Hartz : 8/18/2014
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alopez : 04/05/2019<br>mgross : 08/25/2016<br>mgross : 02/10/2016<br>mcolton : 5/8/2015<br>mgross : 8/21/2014<br>carol : 8/21/2014<br>mcolton : 8/21/2014<br>mcolton : 8/21/2014<br>ckniffin : 8/20/2014<br>mgross : 8/19/2014<br>mcolton : 8/18/2014
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